Carcinomas of the exocrine pancreas in humans usually involve a proliferation of duct-like cells which may be derived from either acinar, islet, or duct cells. The purpose of the proposed research is to examine the consequences of exposing cultured duct tissue prepared from the rat and hamster pancreas to the carcinogens N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 7,12-dimethylbenzanthracene, and 2,2'-dihydroxydiisopropyl nitrosamine (DIPN). Rat pancreatic ducts ranging in size from the common bile/main pancreatic duct to small interlobular ducts have been isolated, characterized biochemically and morphologically, and cultured in a soft agarose matrix for up to 30 days. Further efforts to refine these procedures will be made, and they will be applied to the hamster system. The response of the cultured ducts to exposure to cacinogens will be assessed as a function of time with respect to gross morphological appearance under a dissecting microscope, histology, and scanning and transmission electron microscopy. Biochemical changes will be assessed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate; analysis of the characteristic duct and also enzymes such as gamma-glutamyl transpeptidase which are elevated in human pancreatic cancer. The appearance of oncofetal antigens will be assessed. Finally, the neoplastic potential of the altered ducts will be tested by implantation of the tissues into the athymic nude mouse or syngeneic hosts.